Submicroscopic deletion del(9)(q34.3) is a rare constitutional microdeletion syndrome involving the gene-rich subtelomeric region of the long arm of chromosome 9, with about 30 cases reported.^{1,2,3,4,5,6,7,8,9,10,11,12} Visible constitutional 9q34 deletions are extremely rare, with only a few cases described.^2,10,12 The low prevalence of large terminal deletions at the 9q34 chromosome region in liveborns is thought to reflect lethality in early embryogenesis.¹³

At least 18 patients with 9q34.3 microdeletions detected by fluorescence in situ hybridisation (FISH) testing, in whom normal karyotypes were initially obtained, have been reported.^1,5–7,11 Many patients carry a cryptic del(9)(q34.3) that may result in a clinically recognisable phenotype characterised by severe developmental delay, mental retardation, hypotonia, congenital heart defects (CHD), seizures, and prominent craniofacial features including microcephaly, arched eyebrows, hypertelorism, short nose with anteverted nostrils, open mouth, and a protruding tongue.^6,7,11 Recently, based on clinical and molecular breakpoint analyses using FISH, microsatellites, and single nucleotide polymorphism (SNP) genotyping, two research groups have independently identified an ∼1.0 Mb shortest region of overlap (SRO) of 9q34.3 deletions.^6,11 Although the clinical criteria and incidence of the 9q34.3 deletion are not yet well established, the increasing number of patients reported with del(9)(q34.3) is probably related to the widespread clinical application of telomere FISH. Hence, this microdeletion syndrome may be more common than previously thought.

We have identified a 9q34.3 deletion in each of five unrelated patients, including a patient with clinical features similar to Opitz trigonocephaly C syndrome (OTCS; MIM 211750). A monogenic cause and autosomal recessive mode of inheritance have been considered probable in OTCS, usually associated with a normal karyotype.^14–19 In contrast, several reports on patients with multiple congenital anomalies resembling OTCS and chromosomal …